Independent association of elevated serum hepatocyte growth factor levels with development of insulin resistance in a 10-year prospective study

Clin Endocrinol (Oxf). 2013 Jul;79(1):43-8. doi: 10.1111/j.1365-2265.2012.04496.x. Epub 2013 Mar 25.

Abstract

Objective: Hepatocyte growth factor (HGF) receptors form a hybrid complex with insulin receptors in the liver of mice, which lead to robust signalling to regulate glucose metabolism. Serum HGF levels are high in subjects with metabolic syndrome and/or obesity. Accordingly, we prospectively investigated the relationship between HGF and the development of insulin resistance (IR) in a general population without IR at baseline.

Methods: A total of 1492 subjects received health examinations. After excluding subjects with diabetes and/or IR (n = 402) at baseline, the remaining subjects (n = 1090) were followed-up 10 years later. Complete data sets were available from 716 subjects for prospective analysis. Logistic regression was performed to determine factors associated with the development of IR after 10 years.

Results: In subjects without diabetes at baseline, serum HGF levels were higher (0·26 ± 0·10 ng/ml, n = 259) in subjects with IR than without it (0·22 ± 0·09 ng/ml, n = 1090). After deleting subjects who developed liver disease during follow-up, 188 were found to have developed IR at 10 years after the original screening. HGF (P < 0·05), age (P < 0·001), homoeostasis model assessment index (P < 0·001), HDL-c (P < 0·05; inversely) and hypertensive medication (P < 0·05) were significantly associated with the development of IR by multivariate stepwise logistic regression analysis. A significant (P < 0·05) relative risk [1·75 (95%CI: 1·01-3·12)] for the development of IR was observed in the highest (≥0·30 ng/ml) vs the lowest categories (<0·15 ng/ml) of HGF after adjustments for confounders.

Conclusions: Our 10-year prospective study suggests that elevated serum HGF levels were significantly associated with the development of IR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cholesterol, HDL / blood
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Hepatocyte Growth Factor / blood*
  • Homeostasis
  • Humans
  • Hypertension / physiopathology
  • Insulin Resistance*
  • Logistic Models
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • Cholesterol, HDL
  • Hepatocyte Growth Factor